Epigenetic Predictors of Stroke Recovery

Rajiv Ratan, M.D., Ph.D. and Andrew M. Goldfine, M.D.

Burke Medical Research Institute

Funded in December, 2011: $250000 for 3 years

Identifying predictors of recovery from stroke

Investigators will seek to determine whether there are “epigenetic” predictors present in the blood samples of patients who experience an ischemic stroke that help to explain the tremendous variability in outcomes of stroke recovery.

More than 750,000 patients annually suffer an ischemic stroke when an occlusion occurs in a vessel that ordinarily supplies oxygen-rich blood to brain tissues. Tissues at the infarct site die, but rapid clinical interventions help maintain blood supply to surrounding tissues (the “penumbra”) and spare them. A number of factors have been shown to influence recovery, including: stroke severity, infarct location, age, and functional ability at the time of admission to rehabilitation. Among the most impaired population however, these clinical measures explain less than 50 percent of the variability in recovery outcomes. The investigators hypothesize that “epigenetic” factors account for a proportion of the remaining variability. Epigenetics refers to heritable changes in gene activity. DNA is not changed, but chemical alterations occur in genes, often “silencing” them. Life experiences—such as nutrition, medication history, education and other conditions affecting the brain—converge on a finite set of epigenetic changes that produce “marks” on chromosomes in neurons that can produce effects later in life. The investigators further hypothesize, therefore, that biomarkers for these epigenetic factors can be identified in patients’ blood samples and will correlate with various stroke recovery outcomes.

With the ultimate goal of developing a multi-center stroke biomarker consortium, the Burke investigators plan to draw blood from a pilot sample of 85 ischemic stroke patients and establish a blood registry. They also will collect data on clinical, demographic, and biological factors for each patient, and will then assess the patients’ recoveries from stroke over time. They anticipate that they will be able to identify biomarkers that differentiate patients whose prior environmental influences negatively affect stroke recovery from those whose prior environmental exposures enhance recovery. The investigators anticipate that identifying predictors of recovery variability will enable physicians to provide more reliable prognoses, tailor individual rehabilitation strategies, and promote modifiable behaviors or environmental exposures that may improve recovery patterns. They also anticipate that the findings will lead to the development of more effective therapies.

Significance: This study may lead to more effective tailoring of stroke recovery strategies and identification of pivotal processes that influence brain repair.

Rajiv Ratan, M.D., Ph.D. and Andrew M. Goldfine, M.D.

Dr. Ratan is the Director of the Winifred Masterson Burke/Cornell Medical Research Institute and Burke Professor of Neurology, Neuroscience and Rehab Medicine at Weill Medical College, Cornell University. One focus of Dr. Ratans’ lab is to develop new pharmacological approaches for preventing or ameliorating disability from nervous system conditions. A stroke, spinal cord injury, or other neurological disease will cause neurons to die, which in turn, adversely influences recovery. Much of this neuronal death is caused by highly reactive molecules, called free radicals. Dr. Ratans’ lab is developing “drugs” to augment the body’s natural defenses to free radicals. These drugs are candidate therapies for stroke and spinal cord injury prevention and recovery. Dr. Ratan is not only a member of the Board of Directors of both The Burke Rehabilitation Hospital and the Boston ALS Therapy Alliance but he is also a member of the Scientific Advisory Board of The Boston Cure Project. He is on the Editorial Boards of Antioxidants and Redox Signaling, NeuroRx, The Journal of Neuroscience, Stroke and Neurobiology of Disease. Dr Ratan has written over 60 peer reviewed publications. Dr Ratan received his M.D. and Ph.D. degrees from New York University where he was awarded numerous honors. Before joining Burke, he was an Assistant Professor in the Departments of Neurology and Physical Medicine and Rehabilitation at The Johns Hopkins University School of Medicine and an Associate Professor in the Department of Neurology at Harvard Medical School

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